The primary objectives of this subproject are to test the sequential hypotheses: 1): Protocolized resuscitation is superior to usual care (mean mortality of arms A&B combined < mortality of arm C). 2): The Rivers protocol is superior to the McKendry-Singer protocol (mortality of arm A < mortality of arm B). We propose a prospective, randomized, three-arm parallel-group trial of alternative resuscitation strategies for early septic shock. The three arms are: A. the Rivers protocol; B. the McKendry-Singer protocol; and C. usual care. The primary hypotheses to be tested sequentially are that: protocolized resuscitation results in lower hospital mortality than usual care (arms A & B vs. arm C) and that resuscitation targeted to achieve a normal ScvO2 (Rivers protocol) results in lower hospital mortality than fluid resuscitation and blood pressure control alone (McKendry-Singer protocol) (arm A vs. arm B). These hypotheses will be tested on all enrolled subjects following an intent-to-treat analysis. The study will enroll 1950 subjects at 19 hospitals distributed geographically throughout the US with coordination by the University of Pittsburgh. The study is powered to find a 20% RRR in mortality for both hypotheses.